Karyopherin-? (Kap) proteins mediate the majority of protein transport between the nucleus and the cytoplasm. Of the 20 Kaps in human cells, 11 are import-Kaps or Importins, each recognizing a distinct set of protein cargos. This proposal describes structural, biochemical and biophysical analyses of nuclear import systems for core histones H2A/H2B and H3/H4. Here, we propose to understand how histones H2A/H2B are recognized by their primary human importer Importin-9 (Imp9) and by the homologous yeast Kap114. We will determine the mechanisms of how H2A/H2B is recognized by the Importins, how the GTPase Ran interacts with the Importin- H2A/H2B complex and how histone chaperones affect these interactions. We will also study how histones H3/H4 are recognized by their primary human importer, Importin-4 (Imp4). We will explain how histone chaperone Asf1 contributes to nuclear import of H3/H4 and how RanGTP regulates these multi-protein complexes.